"One More Try" tells the story of Grace (Locsin), a single mom who is forced to reconnect with her son's biological father Edward (Dantes) to save the boy from a worsening rare blood condition.

The source of the cure: a biological sibling to Grace's son, who must be naturally conceived.

In a situation where a child's life is at stake, Grace and Edward's respective relationships -- she has found love anew with Tristan (Marudo); the other is married to Jacqueline (Panganiban) -- take a turn for the worse, as unwanted feelings from the past start to resurface.